Biases incurred from non-random repeat testing of haemoglobin levels in blood donors. Selective testing and its implications

To help prevent anaemia, it is a requisite for blood donors to undergo a haemoglobin test to ensure levels are not too low before donation. It is therefore important to have an accurate testing device and strategy to ensure donors are not being inappropriately bled. A recent study in blood donors used a selective testing strategy where if a donor's haemoglobin level is below the level required for donation, then another reading is taken and if this occurs again, a third and final reading is used. This strategy can reduce the average number of readings required per donor compared to taking three measurements for all donors. However, the final decision‐making measurement will on average be higher than a single measurement. In this paper, a selective testing strategy is compared against other strategies. Individual‐level biases are derived for the selective strategy and are shown to depend on how close a donor's true haemoglobin level is to the donation threshold and the magnitude of error in the testing device. A simulation study was conducted using the distribution of haemoglobin levels from a large donor population to investigate the effects different strategies have on population performance. We consider scenarios based on varying the measurement device bias and error, including differential biases that depend on the underlying haemoglobin level. Discriminatory performance is shown to be affected when using the selective testing strategies, especially when measurement error is large and when differential bias is present in the device. We recommend that the average of a number of readings should be used in preference to selective testing strategies if multiple measurements are available

Copper-Catalyzed Hydrogen/Iodine Exchange in Terminal and 1‑Iodoalkynes

Detailed kinetic profiles of the copper-catalyzed exchange between the acetylenic proton and iodide of terminal and 1-iodophenylacetylenes are reported. The electronic nature of the alkynes does not influence the equilibrium of the exchange (<i>K</i>_eq = 1), only the rate of equilibration. Notably, the profiles are the same for electron-rich, methyl-substituted phenylacetylenes but are divergent for electron-deficient, trifluoromethyl-substituted variants. The heretofore unreported exchange process yields practical considerations regarding reactions involving iodo and terminal alkynes

Tandem Reaction Progress Analysis as a Means for Dissecting Catalytic Reactions: Application to the Aza-Piancatelli Rearrangement

Continuing developments in the elucidation techniques of complex catalytic processes is of foremost importance to modern synthetic chemistry, and the identification of efficient synthetic techniques relies on precise, reliable, and adaptable methods to dissect the mechanism of a given transformation. Currently, methods of reaction development are grounded upon the systematic modification of specific variablessuch as temperature, time, concentration, etc.to account for and control the dynamic series of coupled equilibria within a catalytic environment. On the other hand, tandem reaction analytical methods that involve the concomitant use of different instruments to probe a reaction can provide time-resolved information regarding active chemical species and facilitate the interrogation and optimization of the system. Herein, we report our study applying tandem in situ ReactIR and HPLC-MS monitoring to the dysprosium­(III) triflate-catalyzed aza-Piancatelli rearrangement of 2-furylcarbinols, a reaction that grants access to <i>trans</i>-4,5-disubstituted cyclopentenonescommon motifs in important biologically relevant and natural compounds. With a prototype automated sampling apparatus, information was obtained about the intrinsic chemoselectivity of the reaction, and previously unseen intermediates were observed, allowing for a more detailed reaction mechanism to be substantiated. The advantages of applying this type of tandem measurement to study these types of systems are also discussed

Flow chart of implementation of eHEART and QRISK2 as a prioritisation tool for formal cardiovascular disease assessments.

Abbreviations: BMI, body mass index; CVD, cardiovascular disease; HDL, high density lipoprotein.</p

Codelists and supplementary methods.

ObjectiveTo provide quantitative evidence for systematically prioritising individuals for full formal cardiovascular disease (CVD) risk assessment using primary care records with a novel tool (eHEART) with age- and sex- specific risk thresholds.Methods and analysiseHEART was derived using landmark Cox models for incident CVD with repeated measures of conventional CVD risk predictors in 1,642,498 individuals from the Clinical Practice Research Datalink. Using 119,137 individuals from UK Biobank, we modelled the implications of initiating guideline-recommended statin therapy using eHEART with age- and sex-specific prioritisation thresholds corresponding to 5% false negative rates to prioritise adults aged 40–69 years in a population in England for invitation to a formal CVD risk assessment.ResultsFormal CVD risk assessment on all adults would identify 76% and 49% of future CVD events amongst men and women respectively, and 93 (95% CI: 90, 95) men and 279 (95% CI: 259, 297) women would need to be screened (NNS) to prevent one CVD event. In contrast, if eHEART was first used to prioritise individuals for formal CVD risk assessment, we would identify 73% and 47% of future events amongst men and women respectively, and a NNS of 75 (95% CI: 72, 77) men and 162 (95% CI: 150, 172) women. Replacing the age- and sex-specific prioritisation thresholds with a 10% threshold identify around 10% less events.ConclusionsThe use of prioritisation tools with age- and sex-specific thresholds could lead to more efficient CVD assessment programmes with only small reductions in effectiveness at preventing new CVD events.</div

Age and sex-specific C indices of eHEART in validation cohort.

C-indices and 95% confidence intervals (shown as vertical lines) from eHEART for the prediction of 10-year cardiovascular disease by age and for all ages, in men and women in the validation dataset, Clinical Practice Research Datalink, Hospital Episode Statistics, and the Office for National Statistics, England, United Kingdom, 2004–2019. The overall C-indices account for the discriminatory information in age, hence are higher than the age-specific C-indices.</p

Key characteristics of individuals in CPRD cohort.

Key characteristics of individuals in CPRD cohort.</p

Supplementary tables and figures.

ObjectiveTo provide quantitative evidence for systematically prioritising individuals for full formal cardiovascular disease (CVD) risk assessment using primary care records with a novel tool (eHEART) with age- and sex- specific risk thresholds.Methods and analysiseHEART was derived using landmark Cox models for incident CVD with repeated measures of conventional CVD risk predictors in 1,642,498 individuals from the Clinical Practice Research Datalink. Using 119,137 individuals from UK Biobank, we modelled the implications of initiating guideline-recommended statin therapy using eHEART with age- and sex-specific prioritisation thresholds corresponding to 5% false negative rates to prioritise adults aged 40–69 years in a population in England for invitation to a formal CVD risk assessment.ResultsFormal CVD risk assessment on all adults would identify 76% and 49% of future CVD events amongst men and women respectively, and 93 (95% CI: 90, 95) men and 279 (95% CI: 259, 297) women would need to be screened (NNS) to prevent one CVD event. In contrast, if eHEART was first used to prioritise individuals for formal CVD risk assessment, we would identify 73% and 47% of future events amongst men and women respectively, and a NNS of 75 (95% CI: 72, 77) men and 162 (95% CI: 150, 172) women. Replacing the age- and sex-specific prioritisation thresholds with a 10% threshold identify around 10% less events.ConclusionsThe use of prioritisation tools with age- and sex-specific thresholds could lead to more efficient CVD assessment programmes with only small reductions in effectiveness at preventing new CVD events.</div

Number needed to screen to prevent one event, and number of events captured when prioritising with eHEART in a hypothetical population of 100,000 individuals in England assuming all individuals invited for formal assessment attend.

Number needed to screen to prevent one event, and number of events captured when prioritising with eHEART in a hypothetical population of 100,000 individuals in England assuming all individuals invited for formal assessment attend.</p

Age and sex-specific hazard ratios of eHEART risk predictors with cardiovascular disease in derivation cohort.

Hazard ratios and 95% confidence intervals (shown as vertical lines) for association of cardiovascular disease with: systolic blood pressure, total cholesterol, HDL cholesterol, smoking status, anti-hypertension medication and history of diabetes by age, in men and women in the derivation dataset, Clinical Practice Research Datalink, Hospital Episode Statistics, and the Office for National Statistics, England, United Kingdom, 2004–2019. Hazard ratios are given per standard-deviation increase for SBP, total cholesterol, and HDL cholesterol. Hazard ratios and 95% confidence intervals are shown on the natural log scale.</p